N D Grace

Brigham and Women's Hospital , Boston, Massachusetts, United States

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Publications (44)408.7 Total impact

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    ABSTRACT: Mortality from ST elevation myocardial infarction (STEMI) is decreasing nationwide, but no report to date examined STEMI mortality among patients with cirrhosis.
    Journal of clinical gastroenterology. 10/2014;
  • Sonal Kumar, Norman D Grace, Amir A Qamar
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    ABSTRACT: Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis.
    Digestive Diseases and Sciences 05/2014; · 2.26 Impact Factor
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    ABSTRACT: The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med. 353:2254; 2005). Patients had cirrhosis and portal hypertension but did not have GEV. A total of 90 patients that had baseline day-1 sera available were enrolled into the present study. The objective of this study was to determine whether inflammatory biomarkers in conjunction with clinical parameters could be used to develop a predictive paradigm for HVPG. The correlations between HVPG and IL-1β (P= 0.0052); IL-1R-alpha (P= 0.0085); Fas-R (P=0.0354) and serum VCAM-1 (P= 0.0007) were highly significant. By using multivariate logistic regression analysis and selected parameters (TGFβ; HSP-70; at-risk alcohol use; and Child-Pugh B score) we could exclude HVPG equal or > 12 mmHg with 86 % accuracy ( 95% Confidence Interval; 67.78 to 96.16 %) and the sensitivity was 87.01 % (95% Confidence Interval; 69.68 to 96.34 %). Therefore, the composite test could identify 86 % of compensated cirrhotic patients with HVPG below 12 mmHg and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity and costs in these patients. Our diagnostic test was not efficient in predicting HVPG equal or >12 mmHg. Conclusion: A blood test for HVPG could be performed in cirrhotic patients to prevent unnecessary esophagogastroduodenoscopy. (Hepatology 2013).
    Hepatology 10/2013; · 12.00 Impact Factor
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    ABSTRACT: It remains unclear whether a long-acting preparation of octreotide (Sandostatin LAR) can be safely used for portal hypertension in patients with compensated cirrhosis. To determine the safety and efficacy of LAR among patients with Child Pugh Class A or B cirrhosis and small oesophageal varices. A randomised, double-blind, placebo-controlled study was conducted in 39 patients with cirrhosis and small oesophageal varices. Safety was based on frequency and severity of adverse events. Efficacy was determined by hepatic vein pressure gradient (HVPG) measured at baseline and day 84 following administration of LAR 10 mg (n = 15), 30 mg (n = 10) or saline (n = 14). Fasting and postprandial portal blood flow (PBF), superior mesenteric artery pulsatility index (SMA-PI), glucagon and octreotide levels were measured. An intention-to-treat analysis was performed. Four patients in the LAR 30 group (40%) withdrew from the study due to serious adverse events. No patient in the LAR 10 or control group had serious adverse events. There was no statistically significant decrease between HVPG at day 84 and baseline with LAR 30 mg (11.8 ± 2.3 mmHg vs. 14.1 ± 3.2), LAR 10 mg (15.3 ± 4.8 mmHg vs. 15.1 ± 3.8), or saline (13.3 ± 3.8 mmHg vs. 15.1 ± 4.3) (P = 0.26). Neither PBF, SMA-PI nor plasma glucagon levels were significantly decreased from baseline (P = 0.56). The absence of significant haemodynamic benefit, as well as the high frequency of severe adverse events associated with use of LAR, do not support the use of this agent in the treatment of portal hypertension.
    Alimentary Pharmacology & Therapeutics 03/2012; 35(8):904-12. · 4.55 Impact Factor
  • Norman D Grace
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2011; 9(7):536-8. · 5.64 Impact Factor
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    ABSTRACT: Obesity is associated with an aggressive course in chronic viral hepatitis; however, its impact in the development of clinical decompensation (CD) in patients with established cirrhosis is uncertain. We evaluated the role of obesity, in relationship to other recognized predictors, in the development of CD in patients with compensated cirrhosis. The study population, a subset of patients included in a randomized trial of beta-blockers in the prevention of varices in whom data on body mass index (BMI) was available, consisted of 161 patients with compensated cirrhosis. Laboratory tests and portal pressure (assessed by the hepatic venous pressure gradient or HVPG) were assessed on inclusion. Patients were followed until CD (ascites, hepatic encephalopathy, or variceal hemorrhage), or until September 2002. Altogether, 29% had a normal BMI, 40% were overweight, and 30% were obese. In a median follow-up of 59 months, CD occurred in 48/161 (30%) patients with an increasingly higher rate according to BMI group (15% in those with normal BMI; 31% in overweight; 43% in obese patients, P=0.011). The actuarial probability of developing CD was significantly higher in the abnormal BMI groups (P=0.022). In a multivariate model that included parameters previously identified as being predictive of CD (HVPG, albumin, Mayo endstage liver disease score), etiology, and treatment group, BMI (hazard ration 1.06; 95% confidence interval 1.01-1.12), P=0.02] was an independent predictor of decompensation, together with HVPG and albumin. CONCLUSION: Obesity has a deleterious effect on the natural history of compensated cirrhosis of all etiologies, independent of portal pressure and liver function. Weight reduction may be a valuable therapeutic measure in this patient population.
    Hepatology 05/2011; 54(2):555-61. · 12.00 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
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    A A Qamar, N D Grace
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    ABSTRACT: Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 07/2009; 23(6):441-5. · 1.53 Impact Factor
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    ABSTRACT: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery. Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001). Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2009; 7(6):689-95. · 5.64 Impact Factor
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    ABSTRACT: A total of 213 patients with compensated cirrhosis, portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices. Predictors of the development of hepatocellular carcinoma (HCC), including hepatic venous pressure gradient (HVPG) were analyzed. Baseline laboratory tests, ultrasound and HVPG measurements were performed. Patients were followed prospectively every three months until development of varices or variceal bleeding or end of the study in 09/02. The endpoint was HCC development according to standard diagnostic criteria. Univariate and multivariate Cox regression models were developed to identify predictors of HCC. In a median follow-up of 58 months 26/213 (12.2%) patients developed HCC. Eight patients were transplanted and 28 patients died without HCC. Twenty-one (84%) HCC developed in patients with HCV. On multivariate analysis HVPG (HR 1.18; 95%CI 1.08-1.29), albumin (HR 0.34; 95%CI 0.14-0.83) and viral etiology (HR 4.59; 95%CI 1.51-13.92) were independent predictors of HCC development. ROC curves identified 10 mmHg of HVPG as the best cut-off; those who had an HVPG above this value had a 6-fold increase in the HCC incidence. Portal hypertension is an independent predictor of HCC development. An HVPG >10 mmHg is associated with a 6-fold increase of HCC risk.
    Journal of Hepatology 03/2009; 50(5):923-8. · 9.86 Impact Factor
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    ABSTRACT: Liver biopsy is the gold standard for establishing cirrhosis, but may provide inadequate tissue for interpretation in some patients. The aim of this study was to determine whether the hepatic venous pressure gradient predicts the presence of cirrhosis. Patients with liver disease who had undergone hepatic venous pressure gradient measurements were identified. Clinical, laboratory, and hepatic venous pressure gradient data were collected and biopsies were staged for fibrosis. Univariable logistic regression was used to identify potential predictors of cirrhosis. Multivariable logistic regression was applied to determine adjusted odds ratios. Thirty-two patients were included. The hepatic venous pressure gradient was an independent predictor of cirrhosis. On multivariable analysis, the hepatic venous pressure gradient predicted cirrhosis, with an odds ratio of 1.46 (95% confidence interval 1.05-2.02, P=0.023). Using a cutoff of >or=6.5 mm Hg, the hepatic venous pressure gradient was 86% sensitive and 80% specific for diagnosing cirrhosis. The hepatic venous pressure gradient measurement predicts the presence of cirrhosis in patients with liver disease. Therefore, when the diagnosis of cirrhosis is in question, an elevated hepatic venous pressure gradient can support the diagnosis.
    Journal of Clinical Gastroenterology 03/2008; 42(2):199-203. · 3.20 Impact Factor
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    ABSTRACT: Current guidelines recommend esophagogastroduodenoscopy (EGD) in patients with cirrhosis to screen for gastroesophageal varices (GEV). Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV. There is no agreement regarding a specific platelet count (PLT) that can reliably predict GEV. The present longitudinal study aims to (1) further investigate the relationship between varices and PLT at the time of endoscopy, (2) investigate whether changes in PLT from the baseline over time can predict the development of GEV, and (3) investigate whether changes in PLT correlate with the hepatic venous pressure gradient (HVPG). A secondary analysis was conducted for 213 subjects with compensated cirrhosis with portal hypertension but without GEV enrolled in a randomized, placebo-controlled, double-blind trial of a nonselective beta-blocker used to prevent GEV. PLTs were obtained every 3 months, and HVPG measurements and EGD were done annually. The PLTs were compared between subjects who did and did not develop GEV. In a median follow-up of 54.9 months, 84 patients developed GEV. PLT was greater than 150,000 in 15% of patients at the development of GEV. A receiver operating curve did not show any PLT with high sensitivity or specificity for the presence of GEV. Subjects with clinically insignificant portal hypertension (HVPG < 10 mm Hg) whose PLT remained greater than 100,000 had a 2-fold reduction in the occurrence of GEV (P = 0.0374). A significant correlation was found between HVPG and PLT at the baseline, year 1, and year 5 (P < 0.0001). Conclusion: Cross-sectional or longitudinal evaluations of PLTs are inadequate noninvasive markers for GEV. Patients with mild portal hypertension whose PLT remains greater than 100,000 have significantly less risk of GEV. Although HVPG correlates somewhat with PLT, changes in PLT cannot be used as a surrogate for HVPG changes.
    Hepatology 01/2008; 47(1):153-9. · 12.00 Impact Factor
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    Hepatology 10/2007; 46(3):922-38. · 12.00 Impact Factor
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    ABSTRACT: (Am J Gastroenterol 2007;;102:2086–2102)
    The American Journal of Gastroenterology 10/2007; 102(9):2086-102. · 9.21 Impact Factor
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    ABSTRACT: Our aim was to identify predictors of clinical decompensation (defined as the development of ascites, variceal hemorrhage [VH], or hepatic encephalopathy [HE]) in patients with compensated cirrhosis and with portal hypertension as determined by the hepatic venous pressure gradient (HVPG). We analyzed 213 patients with compensated cirrhosis and portal hypertension but without varices included in a trial evaluating the use of beta-blockers in preventing varices. All had baseline laboratory tests and HVPG. Patients were followed prospectively every 3 months until development of varices or VH or end of study. To have complete information, until study termination, about clinical decompensation, medical record review was done. Patients who underwent liver transplantation without decompensation were censored at transplantation. Cox regression models were developed to identify predictors of clinical decompensation. Receiver operating characteristic (ROC) curves were constructed to evaluate diagnostic capacity of HVPG. Median follow-up time of 51.1 months. Sixty-two (29%) of 213 patients developed decompensation: 46 (21.6%) ascites, 6 (3%) VH, 17 (8%) HE. Ten patients received a transplant and 12 died without clinical decompensation. Median HVPG at baseline was 11 mm Hg (range, 6-25 mm Hg). On multivariate analysis, 3 predictors of decompensation were identified: HVPG (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.05-1.17), model of end-stage liver disease (MELD) (HR, 1.15; 95% CI, 1.03-1.29), and albumin (HR, 0.37; 95% CI, 0.22-0.62). Diagnostic capacity of HVPG was greater than for MELD or Child-Pugh score. HVPG, MELD, and albumin independently predict clinical decompensation in patients with compensated cirrhosis. Patients with an HVPG <10 mm Hg have a 90% probability of not developing clinical decompensation in a median follow-up of 4 years.
    Gastroenterology 08/2007; 133(2):481-8. · 12.82 Impact Factor
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    Norman D Grace, Lyle B Dennis
    Hepatology 07/2007; 45(6):1337-9. · 12.00 Impact Factor
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    ABSTRACT: A prospective randomized trial was undertaken to test the efficacy of low and standard doses of pegylated interferon alpha-2b in combination with ribavirin for the initial treatment of chronic hepatitis C. By nature of its design the study also provided data on response to therapy over a spectrum of doses of both pegylated interferon alpha-2b and ribavirin calculated on a body weight basis. Fifty micrograms of pegylated interferon alpha-2b or 100 microg for patients weighing<75 kg or 150 microg for patients>or=75 kg were administered weekly with 1000 mg ribavirin daily for 48 wk if serum hepatitis C virus (HCV) RNA was undetectable after the first 24 wk of therapy. Overall sustained viral response (SVR) was 45% for standard dose and 33% for low dose, p=0.02. For genotypes 2 and 3 SVR was 65% for standard dose, and 56% for low dose, p=0.51. For genotype 1 SVR was 38% for standard dose, and 24% for low dose, p=0.03. For genotype 1 patients whose doses exceeded the 1-2-5 threshold, that is >or=1.25 microg/kg body weight pegylated interferon alpha-2b weekly and >or=12.5 mg/kg body weight ribavirin daily, SVR was 51%. The results of this study underscore the importance of adequate dosing of ribavirin as well as pegylated interferons in achieving an SVR when treating genotype 1 chronic hepatitis C patients with combination therapy.
    The American Journal of Gastroenterology 06/2006; 101(6):1268-73. · 9.21 Impact Factor
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    ABSTRACT: Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown. We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients). The primary end point was the development of gastroesophageal varices or variceal hemorrhage. Endoscopy and HVPG measurements were repeated yearly. During a median follow-up of 54.9 months, the rate of the primary end point did not differ significantly between the timolol group and the placebo group (39 percent and 40 percent, respectively; P=0.89), nor were there significant differences in the rates of ascites, encephalopathy, liver transplantation, or death. Serious adverse events were more common among patients in the timolol group than among those in the placebo group (18 percent vs. 6 percent, P=0.006). Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year. Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events. (ClinicalTrials.gov number, NCT00006398.)
    New England Journal of Medicine 12/2005; 353(21):2254-61. · 54.42 Impact Factor
  • Norman D. Grace, Richard S. Tilson
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    ABSTRACT: Portal hypertension is responsible for the major complications of cirrhosis including the development of ascites, variceal hemorrhage, portal systemic encephalopathy, and the hepatorenal syndrome. Until the late 1970s, surgically created shunts were the primary treatment for the complications of portal hypertension. Although shunts successfully lowered portal pressure, they were complicated by progressive liver failure, hepatic encephalopathy, and, in the case of primary prophylaxis, an increase in mortality compared to supportive medical treatment (1). Endoscopic sclerotherapy was popularized in the 1970s and 1980s as the primary medical therapy for the control of initial variceal hemorrhage and the prevention of recurrent hemorrhage. Sclerotherapy for primary prophylaxis was extensively studied in randomized controlled trials (RCT) but two very well designed RCTs had to be terminated by the external monitoring committees because of a higher mortality in patients treated with sclerotherapy when compared to a medical control group (2). Most recently, sclerotherapy has essentially been replaced by endoscopic variceal ligation. However, endoscopic therapy does not alter portal pressure and is ineffective for nonesophageal variceal hemorrhage and portal hypertensive gastropathy.
    12/2004: pages 199-219;
  • Hepatology 01/2003; 38:206-206. · 12.00 Impact Factor

Publication Stats

2k Citations
408.70 Total Impact Points

Institutions

  • 2001–2013
    • Brigham and Women's Hospital
      • • Center for Brain Mind Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2007
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1998–1999
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1991
    • Tufts University
      • Department of Medicine
      Medford, MA, United States
  • 1986
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 1985
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1984
    • Lemuel Shattuck Hospital
      Jamaica Plain, Massachusetts, United States